BIOLOGICAL METHYLATION

SummaryThe enzymatic methylation or demethylation of naturally occurring compounds represents significant metabolic processes which have gained additional interest since the discovery of a mechanism by means of which methyl groups can be transferred from one compound to another.The capacity to transfer methyl groups is confined to a fewN‐and S‐methylated compounds; methyl groups linked to C atoms, however, have not been found to be transferable but are known in some cases to be oxidized. OtherN‐methylated compounds, such as sarcosine, the methylated ammonium bases, the α‐ and γ‐betaines of amino‐acids other than glycine, are unable to take part in the methyl exchange in either direction, but are oxida‐tively demethylated by the organism or excreted unchanged. Choline, methionine, and to a lesser degree betaine, play a major part in transmethylation; these compounds are needed for the maintenance of growth and for the prevention of fatty infiltration of the liver, kidney haemorrhage, liver cirrhosis, or perosis. Since choline can methylate homocysteine to methionine in the organism and conversely methionine and betaine are able to supply methyl groups for the methylation of ethanol‐amine to choline, a system of continuous interchange of methyl groups is established and a ‘pool’ of labile methyl groups is formed. This ‘pool’ also acts as a source of methyl supply for other compounds such as creatine, methylnicotinamide, anserine and possibly others, but these latter compounds have not been shown to act as ‘methyl donors’. The role of glycine and of methylated purines as methylating agents is controversial.The liver is the main site of methylation, though kidney and muscle tissue were found to catalyse methylation in a few cases. The chemical mechanism of methylation and demethylation has not yet been clarified. Oxidation prior to demethylation is believed to take place in the case of methionine. A methyl synthesis from unmethylated sources is possible but not probable; as a consequence methylated compounds with labile methyl groups must be regarded as essential dietary factors.The physiological significance of the numerous naturally occurringN‐methylated compounds is further enhanced by their pharmacological effects and by their relationship to hormones. The latter manifests itself in the preponderant occurrence of many methylated compounds at the sites of hormonal activities connected with reproduction, and conversely by the alleged effect of some hormones on methylating activities. Thus it is not unreasonable to picture an influence of methylating reactions on the regulatory activities of hormones leading in pathological cases to a derangement of the hormonal balance and possibly to abnormal growth conditions such as malignancy.I wish to express my gratitude to Dr E. M. Crook, Kothamsted Experimental Station, for reading the manuscript and for valuable criticism.